Fast repair of O6-ethylguanine, but not O6-methylguanine, in transcribed genes prevents mutation of H-ras in rat mammary tumorigenesis induced by ethylnitrosourea in place of methylnitrosourea.

ABSTRACT: Differential repair of structurally distinct mutagenic lesions in critical genes may influence the cellular risk of malignant conversion. We have investigated rat mammary tumorigenesis induced by N-ethyl-N-nitrosourea (EtNU) versus N-methyl-N-nitrosourea (MeNU) with respect to tumor incidence, ras gene mutation, and gene-specific repair. Both carcinogens induced mammary adenocarcinomas at high yield. In mammary epithelia (very low expression of O6-alkylguanine-DNA alkyltransferase, MGMT), O6-methylguanine (O6-MeGua) was eliminated from transcribed (H-ras and beta-actin) and inactive genes (IgE heavy chain) at the same slow rate as determined for bulk genomic DNA. The persistence of O6-MeGua in DNA correlated with a high frequency of G:C --> A:T transition mutations at codon 12 of the H-ras

SUBMITTER: Engelbergs J 

PROVIDER: S-EPMC19127 | biostudies-literature | 1998 Feb

REPOSITORIES: biostudies-literature